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Les enfants atteints d’un cancer sont régulièrement confrontés à des procédures douloureuses au cours de leur prise en charge. Afin de les accompagner au mieux dans leurs soins, des techniques de communication dérivées de l’hypnose ont montré d’excellents niveaux d’efficacité sur la réduction de la détresse et de la douleur associées à ces procédures. Nous avons mené une étude préliminaire évaluant les effets d’une formation à la communication hypnotique sur la pratique des infirmières lors de procédures douloureuses auprès d’enfants atteints d’un cancer. Les résultats ont montré une bonne acquisition des techniques par les infirmières et des effets importants de ces techniques sur les niveaux de douleurs et de détresse des enfants. Cette étude a aussi permis de récolter des recommandations d’amélioration de la formation pour développer un design plus simple de la formation Rel@x, qui sera testée auprès d’un échantillon d’infirmières et de patients plus important.

Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation. A major advance consisted of the identification of the alternative complement pathway in the pathogenesis of aHUS, thus paving the way for the use of the C5a inhibitor eculizumab in this indication. Eculizumab has thereafter dramatically improved the management of patients affected with aHUS. During spring 2011, a great epidemic of entero-hemorrhagic Escherichia coli (EHEC) associated HUS occurred in Germany, providing clinicians the opportunity to examine the relevance of antibiotic prophylaxis, plasma exchange and eculizumab in EHEC-associated HUS. In this work, we herein present advances achieved in the setting of therapeutic management and prognosis in HUS and other related TMA syndromes.

Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature. HUS can result from toxins stemming from bacterial infections of the digestive tract, alternate complement pathway abnormalities, metabolic or coagulation disorders or, lastly, drug and various toxic compounds. The diverse forms of HUS reflect the insights gained in the understanding of the pathophysiological mechanisms underpinning TMA. In this first part, a broad overview of the epidemiological, physiopathological and clinical aspects of HUS and related TMA syndromes is presented.

During normal pregnancy, renal blood flow and GFR increase gradually until they reach a peak of about 150% of their normal values by the end of the 1st trimester. This increase in GFR is secondary to the extra-cellular compartment expansion caused by a positive sodium balance of about 500–900 mmol which is in turn associated with a water retention amounting 6 to 8 liters. Blood pressure decreases during a normal pregnancy because of the decrease in peripheral vascular resistance. This drop in blood pressure is limited by the renin-angiotensin system. Blood pressure gradually recovers during the 3rd trimester. Systemic hypertension, proteinuria > 0.3 g/day and edema are the usual signs leading to the diagnosis of PE. However, any of the above listed signs found in isolation can be a tell tale sign of PE and must therefore prompt for the identification of a possible fetal effect The differential diagnosis of PE includes essential hypertension and hypertension secondary to a pre-existing renal failure. In the latter, signs of renal impairment early in the pregnancy, or (and) renal failure prior to the pregnancy are of important diagnostic clues. Causes of acute renal failure during pregnancy are numerous. PE associated acute renal failure presents in 5–10% of severe forms of PE. This is always a bad prognostic sign with a predicted mortality of 10%. Histological features are those of acute tubular necrosis with “endotheliosis” an inflammation of the glomerular endothelium. This renal impairment is frequently complicated by pulmonary edema. Passed the acute phase, the recovery of the renal function is usually complete. An acute renal failure during pregnancy can also be secondary to a pre-existing renal impairment suddenly aggravated by PE. In this setting, the probability of these patients requiring long term dialysis is high. Post-partum Haemolytic-Uremic Syndrome (HUS), although rare, is a serious condition which, following delivery, will require an early diagnosis (haemolysis, hypertension, acute renal failure) and urgently require symptomatic, perhaps specific, treatment (Plasma exchange transfusion).

Summary. Tests for a dysimmune state were done in an unselected group of 67 patients with agnogenic myeloid metaplasia (AMM). The results were compared to those of 56 patients with polycythaemia vera (PV). 75% of AMM patients versus 32% of PV patients had various abnormalities. The most frequent disorders among AMM patients were serum antinuclear and anti smooth muscle autoantibodies (10 3% each), a positive test for rheumatoid factor (21 7%), a polyclonal increase in serum immunoglobulin levels (46 8%) or a serum monoclonal component (9 7%), a positive direct Coombs’test (19%), an anti I autoantibody (30%). In AMM patients there was no relationship between age, sex, importance of splenic enlargement, time from diagnosis or treatment and the present of a dysimmunity. Furthermore, in AMM patients, but also in PV patients, it seems that the more frequent and numerous these abnormalities the more severe is the myelofibrosis. Like other previous studies, these results suggest a lymphoid cell involvement in AMM and a role for these immune disorders in the pathogenesis of myelofibrosis.

To determine if parathyroid hormone release in man is directly stimulated by glucocorticoids, dispersed human parathyroid cells from hyperplastic glands obtained from eight renal transplant recipients were studied in vitro. Dexamethasone (10(-11) to 10(-6) mol l-1) increased PTH release in a time- and dose-dependent manner. A plateau was reached at 10(-8) mol l-1 (1015 +/- 149 vs. 230 +/- 27 pg 10(-4) cells for control value, after 24 h incubation; P less than 0.0001). An interaction with a glucocorticoid receptor was suggested since 10(-6) mol l-1 RU 486 blunted the dexamethasone-induced PTH release. By Northern blot analysis, dexamethasone was found to increase the amount of preproPTH mRNA in these cells. The effect of dexamethasone was probably at the gene level since (1) 1,25 dihydroxy vitamin D3 inhibited both iPTH and preproPTH mRNA increases induced by dexamethasone and (2) alpha-amanitin (1,25 micrograms ml-1) also completely suppressed the dexamethasone-induced PTH release. Thus, for the first time, we demonstrate that dexamethasone induces an increase of PTH synthesis, probably by increasing PTH gene transcription. This effect may play an important pathogenic role in persisting hyperparathyroidism and steroid-induced bone complications in renal transplant recipients.

Thrombotic microangiopathies (TMA) represent rare diseases requiring a high skill for their management that deserved in France the identification of a dedicated National reference center. TMA are short-term life-threatening diseases; however, with an adapted management, their prognosis can be excellent. It is therefore mandatory to recognize and treat them rapidly according to standard guidelines. Telemedicine is a specialized hub consisting of highly skilled staff trained in a specific domain of medicine. The telemedicine activity of a reference center is an important representative indicator of its expertise and recourse ability. It requires to be accurately evaluated and promoted. In this work, we report the French reference center for TMA telemedicine activity since its setting-up. TMA represent an interesting model of diseases that required a specific organization of telemedicine activity to adapt to clinicians demand, which includes particularly the need to answer resorts in real time 24/7.

Candiduria may be a marker of serious fungal infections such as pyelonephritis. With the exception of fluconazole and flucytosine, antifungals drugs are not excreted into the urine as active drugs, making the management of infection due to fluconazole-resistant Candida difficult. We report a case of recurrent Candida parapsilosis candiduria in a kidney transplant recipient suffering from chronic ureteral obstruction requiring permanent ureteral catheterization (double-J stent). Attempts to remove the stent led to pyelonephritis episodes during which only Candida was isolated from the urine. Following several courses of azole-based therapy, the causative agent became resistant to fluconazole. Clinical and mycological cure were obtained combining irrigations of caspofungin through a percutaneous calicostomy catheter and oral flucytosine. This strategy may represent an interesting therapeutic alternative in case of fluconazole-resistant symptomatic candiduria.

Resume L'apparition, il y a 20 ans de cela, des inhibiteurs de la calcineurine, a transforme le pronostic de la transplantation renale et en a fait un traitement de choix de l'insuffisance renale terminale. Aujourd'hui, meme des patients a haut risque immunologique peuvent etre greffes, grâce a des combinaisons de plus en plus sophistiquees de traitements immunomodulateurs, permettant d'etendre la liste des donneurs et des receveurs potentiels. Grâce a une meilleure prevention du risque de rejet aigu et des complications infectieuses precoces, la survie des greffons a un an est de l'ordre de 95 %. Assurer la survie des patients et la fonction du greffon a long terme est donc progressivement devenu le principal defi. Seule une meilleure maitrise de la toxicite chronique des immunosuppresseurs, couplee a une acquisition de la tolerance de l'allogreffe renale, permettront de le relever.

Idiopathic membranous glomerulonephritis (MGN) is an immune complex nephropathy characterized by the subepithelial deposition of immunoglobulin (Ig)G. The pathogenesis of the disease remains largely unknown, but recent evidence suggests that human MGN may involve an autoimmune component. In the present study, we have analyzed the IgM and IgG antibody repertoires of patients with MGN towards self- and nonself-antigens using a technique of quantitative immunoblotting on a panel of whole human tissue or solubilized bacterial cell extracts as sources of antigens. Data were compared by means of multiparametric statistical analysis. We demonstrate that the antibody repertoires of self-reactive IgM and IgG in plasma of patients with MGN exhibit significantly altered patterns of reactivity, as compared with those of healthy controls. In contrast, multiparametric statistical analysis does not discriminate the reactivity patterns of IgM and IgG in plasma of patients and healthy controls towards nonself antigens. These observations indicate that a failure in the regulation of physiological self-reactivity is associated with immune complex nephropathy in MGN.

Nowadays organ transplantations suffer from a lack of donors. Thus the waiting list of patients is constantly growing. Several ways to increase organ procurement are being evaluated. About 50% of cerebral deaths are related to vascular cerebral in patients older than 60 years. For the last few years, organs have been harvested from these patients despite their age. As the quality of the grafts is reduced, transplantation of one kidney may be insufficient whilst transplantation of the two kidneys to the same recipient is technically possible. We report here a case of a 44-year-old patient who was transplanted with two kidneys in September 2000. The donor was 85-year-old patient who died after prolonged cardiac arrest. Kidney biopsy showed a 16% rate of sclerotic glomeruli and mild interstitial fibrosis. The creatinine clearance estimated by the Cockcroft formula was 50 mL.min-1. The double kidney transplantation was successful, without any surgical or anaesthetic complication. Restoration of urine production was immediate. Three months after the transplantation, creatinine clearance was 80 mL.min-1. This observation gives the opportunity to discuss the criteria for organ harvesting in patients with cerebral death. Donor age should not remain anymore a systematic contra indication for kidney or liver donation. Renal function, macroscopic examination and histological findings seem more important for making a decision in taking the graft. Double transplantation, here the second case in France, has been performed for several years in other countries, and has permitted to expand the pool of donors, thus increasing the number of transplanted patients.

Resume Une pseudohyperchloremie a fait suspecter une intoxication par les bromures chez un patient presentant des troubles psychiques. Le diagnostic a ete confirme par une bromuremie superieure a 20 mmoL·L–1. La seule rehydratation a permis de baisser le taux de brome sanguin et de normaliser la chloremie. Dans ce type d’intoxication, une hyperchloremie associee a un trou anionique negatif constitue la cle du diagnostic.

Urinary tract infections (UTIs), the most common form of bacterial infection in kidney transplant recipients, recently have been demonstrated to be detrimental for long-term graft outcome. Therefore, reinforcing antibiotic prophylaxis might be vital, in addition to basic hygiene recommendations, surgical care, and prophylaxis by trimethoprim-sulfamethoxazole.In 2006, a Legionella pneumophila contamination of our department's water pipes meant that all the patients undergoing renal transplantation underwent a 1-month regimen of ofloxacin (OFLO) (200 mg every other day). We took this opportunity to measure the incidence of UTI, including acute pyelonephritis (APN), in 100 consecutive patients transplanted before (n = 50) and after (n = 50) this treatment decision was reached. We also studied the antimicrobial resistance profiles in our department and in the rest of the hospital.No patient developed Legionnaire's disease. A dramatic decrease in the incidence of UTI (-63%) was also seen in patients undergoing OFLO treatment. Logistic regression analysis demonstrated that the use of OFLO was independently associated with a reduction in UTI (odd ratio [OR] = 0.31%, 95% confidence interval [CI] 0.11-0.84, P = 0.02) and APN (OR = 0.21%, 95% CI 0.07-0.98, P = 0.045). This protection was sustained during the whole first year post transplantation. As for resistance rates, we observed a decrease in the susceptibility of Pseudomonas aeruginosa to ciprofloxacin in our nephrology department, compared with that observed in the rest of the hospital. The incidence of multi-resistant bacteria was stable.Our unintentional extension of prophylactic antibiotherapy with OFLO gave rise to a dramatic decrease in the 1-year incidence of UTI and APN in kidney recipients. Emergence of resistant strains is, however, a major concern.

During normal pregnancy, renal blood flow and GFR increase gradually until they reach a peak of about 150% of their normal values by the end of the 1(st) trimester. This increase in GFR is secondary to the extra-cellular compartment expansion caused by a positive sodium balance of about 500-900 mmol which is in turn associated with a water retention amounting 6 to 8 liters. Blood pressure decreases during a normal pregnancy because of the decrease in peripheral vascular resistance. This drop in blood pressure is limited by the renin-angiotensin system. Blood pressure gradually recovers during the 3(rd) trimester. Systemic hypertension, proteinuria0.3 g/day and edema are the usual signs leading to the diagnosis of PE. However, any of the above listed signs found in isolation can be a tell tale sign of PE and must therefore prompt for the identification of a possible fetal effect The differential diagnosis of PE includes essential hypertension and hypertension secondary to a pre-existing renal failure. In the latter, signs of renal impairment early in the pregnancy, or (and) renal failure prior to the pregnancy are of important diagnostic clues. Causes of acute renal failure during pregnancy are numerous. PE associated acute renal failure presents in 5-10% of severe forms of PE. This is always a bad prognostic sign with a predicted mortality of 10%. Histological features are those of acute tubular necrosis with "endotheliosis" an inflammation of the glomerular endothelium. This renal impairment is frequently complicated by pulmonary edema. Passed the acute phase, the recovery of the renal function is usually complete. An acute renal failure during pregnancy can also be secondary to a pre-existing renal impairment suddenly aggravated by PE. In this setting, the probability of these patients requiring long term dialysis is high. Post-partum Haemolytic-Uremic Syndrome (HUS), although rare, is a serious condition which, following delivery, will require an early diagnosis (haemolysis, hypertension, acute renal failure) and urgently require symptomatic, perhaps specific, treatment (Plasma exchange transfusion).

It is shown that the electrical breakdown voltages of polycarbonate film/metal foil capacitors can be increased. This can be achieved by briefly exposing the metal foil in these spirally wound film foil sections to a low-pressure, low-temperature gas plasma. Exposure of tin/lead foil to a 96% CF/sub 4//4% O/sub 2/ gas plasma for four min, for example, produced >500% increase in breakdown voltage of sealed polycarbonate capacitors. >

McArdle's disease is an autosomal recessive glycogenosis caused by deficiency of muscle glycogen phosphorylase resulting in glycogen accumulation in the skeletal muscle. Typically, McArdle's disease is characterized by exercise intolerance with muscle cramps and myoglobinuria.We report a 20-year-old woman with massive rhabdomyolysis and acute renal failure revealing a McArdle's disease.Although muscle impairment is constant in McArdle's disease, massive rhabdomyolysis with severe acute renal failure has been rarely reported as a presenting feature. The mechanisms and therapeutic implications of renal injury are discussed.

We report a case of severe ketoacidosis. Initially the patient showed metabolic acidosis, the anion gap was positive and there was neither hyperlactatemia nor intoxication with acid substances. As the rate of glycemia was high (17.8 mmol/L), the diagnosis of diabetic ketoacidosis was proposed. Under treatment with continuous IV injection of insulin, hypoglycemia (1.8 mmol/L) appeared rapidly, while urine bioreactive test was positive for ketonuria, but negative for glycosuria. We finally concluded that it was an alcoholic ketoacidosis. The history of the patient confirmed the diagnosis : chronic alcoholism with recent increased of alcohol intake which provoked vomiting and fasting. This case report shows the difficulty in distinguishing between alcoholic ketoacidosis and diabetic ketoacidosis. We discuss the diagnostic strategy and particularly biologic data in the light of pathophysiologic mechanism of alcoholic ketoacidosis.

Hemophagocytic lymphohistiocytosis syndrome (HLS) is defined by activated macrophage proliferation. These cells phagocyte the blood elements. This syndrome can be primary as an autosomal recessive disease or secondary to neoplasia, immune diseases or infections-viral, parasitary or bacterian.Our case concerns an association of HLS and Escherichia coli (E. coli) sepsis in a metastatic prostatic cancer. The evolution was rapidly improved by antibiotics alone. The clinical and biological aspects as well as the differential diagnosis are discussed.The HLS is fatal. It can be caused by a severe infection, even an E. coli sepsis. The treatment focused on etiology can be sufficient.

Breakdown voltage of wound, polymer-film/metal-foil capacitors have been dramatically increased by briefly exposing them (after they had been spirally wound) to a low-pressure, low-temperature gas plasma. Exposure of wound polycarbonate-based capacitors to a 96%CF/sub 4//4%O/sub 2/ gas plasma for 4 min, for example, produced a 200% increase in breakdown voltage, while exposure of similarly constructed polyester-and polypropylene-based capacitors to the same gas plasma showed more modest 23% and 4% improvements, respectively, in breakdown voltages. >

The information system usually implies the use of the entity-relationship formalism at conception level and database for the implementation aspect. But the information is not only located in the database but also in the communication system. During the information system design, the conceptual stage is not changed. At the logical step which describes the data organization, both database and communication aspects are taken into account. The logical analysis must generate the database structures and the manufacturing message specifications (MMS) configuration of all equipment which corresponds to the physical stage. Some concrete rules which permit translation of the entity relationship formalism to MMS objects and MERISE communication model to organize each VMD are presented. >

The new work organisations in companies are based more and more on computerized environments (groupware, CSCW, workflow...) and consequently lead to an increase in the use of communications resources. Thus, a bad evaluation of the company network capabilities can generate dysfunction of group conversations. The objective of this paper is to improve the network organization in order to improve the quality of service that it can guarantee. A method based on the analysis of cooperation graphs is proposed. The interests of this method are shown from the network organization simulation results of an exchange scenario.

A false hyperchloremia in a patient with a history of depression suspected bromide intoxication. The diagnosis was confirmed by an increased bromide concentration20 mmoL.L-1. Rehydration was effective and allowed to decrease bromide concentration. In conclusion, hyperchloremia associated with a negative anion gap is a clue to the diagnosis.

Hemolytic-uremic syndrome (HUS) is a rare disease but may be fatal in the absence of appropriate treatment. It is the first cause of acute renal failure (ARF) in children and is less frequently observed in adults. We report the case of a 50 years old woman who was first admitted in the surgery department for intestinal occlusion. Haematological and renal disorders were not recognised initially. Specific treatment with plasma exchanges was beneficial. This case was idiopathic but in 50% of HUS in adults, an aetiology can be found and sometimes treated: drugs, pregnancy, systemic diseases, hypertension or cancer. Although still debated, treatment is based on fresh frozen plasma infusion, associated or not to plasma exchanges. Some other therapies can be added: steroids, polyvalent immunoglobulin infusion, vincristin or splenectomy. In all cases, blood pressure control must be obtained, especially with ACE inhibitors. Response to treatment is often excellent, but chronic renal failure persists in about 25% of cases in adults. Recurrences are rare and occur mainly in patients with an hereditary factor H deficiency. The hemolytic-uremic syndrome should be diagnosed and treated immediately.

Nowadays organ transplantations suffer from a lack of donors. Thus the waiting list of patients is constantly growing. Several ways to increase organ procurement are being evaluated. About 50% of cerebral deaths are related to vascular cerebral in patients older than 60 years. For the last few years, organs have been harvested from these patients despite their age. As the quality of the grafts is reduced, transplantation of one kidney may be insufficient whilst transplantation of the two kidneys to the same recipient is technically possible. We report here a case of a 44-year-old patient who was transplanted with two kidneys in September 2000. The donor was 85-year-old patient who died after prolonged cardiac arrest. Kidney biopsy showed a 16% rate of sclerotic glomeruli and mild interstitial fibrosis. The creatinine clearance estimated by the Cockcroft formula was 50 mL.min-1. The double kidney transplantation was successful, without any surgical or anaesthetic complication. Restoration of urine production was immediate. Three months after the transplantation, creatinine clearance was 80 mL.min-1. This observation gives the opportunity to discuss the criteria for organ harvesting in patients with cerebral death. Donor age should not remain anymore a systematic contra indication for kidney or liver donation. Renal function, macroscopic examination and histological findings seem more important for making a decision in taking the graft. Double transplantation, here the second case in France, has been performed for several years in other countries, and has permitted to expand the pool of donors, thus increasing the number of transplanted patients.

Idiopathic membranous glomerulonephritis (MGN) is an immune complex nephropathy characterized by the subepithelial deposition of immunoglobulin (Ig)G. The pathogenesis of the disease remains largely unknown, but recent evidence suggests that human MGN may involve an autoimmune component. In the present study, we have analyzed the IgM and IgG antibody repertoires of patients with MGN towards self- and nonself-antigens using a technique of quantitative immunoblotting on a panel of whole human tissue or solubilized bacterial cell extracts as sources of antigens. Data were compared by means of multiparametric statistical analysis. We demonstrate that the antibody repertoires of self-reactive IgM and IgG in plasma of patients with MGN exhibit significantly altered patterns of reactivity, as compared with those of healthy controls. In contrast, multiparametric statistical analysis does not discriminate the reactivity patterns of IgM and IgG in plasma of patients and healthy controls towards nonself antigens. These observations indicate that a failure in the regulation of physiological self-reactivity is associated with immune complex nephropathy in MGN.

Plasminogen activator inhibitor type 1 plays a prominent part in the regulation of extra and intra-vascular fibrinolysis through the inhibition of plasmin formation. In addition to its role in the resolution of blood clots, PAI-1 is involved in a variety of other biological processes including extracellular remodeling, cellular mobility, embryo implantation, development and tumoral proliferation. Moreover, PAI-1 is also implicated in various pathological processes such as thromboembolic diseases, atherosclerosis and fibrosis formation, particularly in the kidney and the lung. Inhibition of PAI-1 activity or of PAI-1 synthesis by specific antibodies, peptidic antagonists, antisens oligonucleotides or decoy oligonucleotides has been obtained in vitro but need to be evaluated in vivo. All these findings may have new therapeutical implications, explaining the importance of studies on PAI-1 production and regulation.

This is the first retrospective study aimed to analyze the clinical symptoms, the etiology, the morbidity and the lethality of acute renal failure in patients over 80 years. The criterion of inclusion was the occurrence of acute renal failure defined on the basis of high plasma creatinine associated with normal kidney size in patients of this class of age who had been hospitalized in an intensive care unit between October 1971 and September 1996. In the case of a preexisting moderate nephropathy, acute renal failure was defined by an increase of plasma creatinine of at least 50% over its basal value. Three hundred and eighty-one patients over 80 years out of a total of 2,111 patients with acute renal failure were included in this study. The various etiologies and mechanisms of the disease are described. Twenty-nine% of the patients underwent dialysis. The global lethality reached 40% during the time of hospitalization. The factors significantly associated with a poor prognosis were identified as cancer essentially, but also sepsis and preexisting cardiovascular diseases. The mean survival after hospitalization was of 19 months. In summary, the frequency of admission for acute renal failure of patients over eighty in intensive care units is increasing but the rate of lethality observed is less than expected. A pattern of pathological associations leading to death in these patients cannot be defined with certitude. Therefore, the methods of renal replacement therapy available in modern intensive care units must be utilized in this class of age as it is the case in younger patients.

Tissue-specific expression patterns of the paired type IV collagen genes COL4A5 and COL4A6 form the basis for organ involvement in X-linked Alport syndrome, a disorder in which these genes are mutated. We investigated the proximal promoter region of COL4A5 and COL4A6 using glomerular visceral epithelial cells, in which COL4A5 alone is transcribed; keratinocytes, in which the genes are co-transcribed; and additional model cell lines. By RNase protection assays, the intergenic region is 292 base pairs. Transcription start sites for two 5' splice variants of COL4A6 are 1 kilobase apart. Transient transfections with reporter gene constructs revealed that the minimal promoters for COL4A5 and COL4A6 are within 100 base pairs of their respective transcription start sites and are functionally distinct. In further transfection, gel shift and footprinting assays, we defined a bidirectional positive regulatory element, which functions in several cell types, but not in glomerular visceral epithelial cells selectively transcribing COL4A5. The existence of separate promoters for COL4A5 and COL4A6 permits fine control over their expression. Activation through the bidirectional element can bring about co-expression of the genes, exploiting their paired arrangement. Features of the proximal promoter region frame its roles in a hierarchy regulating type IV collagen gene expression.

Renal impairment, usually due to tubulointerstitial and rarely glomerular disorders occurs in 10 to 30% of patients with primary Sjögren's syndrome. Extracapillary proliferation may also be observed.A 62-year-old woman with primary Sjogren's syndrome diagnosed 12 years earlier, developed microscopic polyangeitis leading to rapidly progressive renal failure. Antipolynuclear anticyclosine antibody (ANCA) serology was positive (pANCA, anti MPO) and the renal biopsy evidenced necrotizing glomerulonephrities with extracapillary proliferation. Outcome was favorable despite a recurrence one year after onset.Extracapillary proliferative glomerulonephritis is characterized by hematuria and proteinuria associated with renal failure. Renal impairment may worsen rapidly, sometimes leading to an emergency situation because the renal prognosis is directly related to delay to treatment. This case illustrates an uncommon complication of Sjögren's syndrome, compared with the usual tubulointerstitial disorders. The mechanism remains unknown, but outcome can be favorable with rapidly initiated immunosuppressor treatment.

Hemolytic uremic syndrome (HUS) is a rare complication in solid organ transplantation. It can be associated with severe hypertension. Several risk factors have been identified including immunosuppressive drugs such as cyclosporin A and, more recently, tacrolimus.Here we report a case of tacrolimus-induced HUS in a 61-yr-old woman after liver transplantation. Hypertension, microangiopathic anemia and end-stage renal failure occurred 2 yr after liver transplantation.At admission, she had malignant hypertension with a severe hypertensive retinopathy, renal failure (creatininemia: 800 micromol/L) and microangiopathic anemia (Hb: 7.3 g/dL, a low platelet count and elevated lactate dehydrogenase). At renal biopsy, histologic findings were ischemic and sclerotic glomeruli with hyaline thrombi, severe mesangiolysis and interstitial fibrosis.Despite steroid treatment, antihypertensive agents and fresh frozen plasma therapy, end-stage renal failure was observed and chronic hemodialysis treatment was required.

Hemolytic uremic syndrome (HUS) is an uncommon cause of end-stage renal failure in adults, and few data are available concerning the outcome of renal transplantation in these patients. We conducted this retrospective multicentric study to appreciate the outcome of adult renal transplant recipients whose primary disease was HUS. Sixteen patients, transplanted between 1975 and 1995, were included in the study. In each case, initial diagnosis of HUS was documented by a kidney biopsy. These 16 patients received a total of 25 allografts: 1 graft for 9 patients, 2 grafts for 5 patients, and 3 grafts for 2 patients. Nine patients (56%) developed definite clinical and pathologic evidence of recurrence on at least 1 graft. Four additional patients (25%) demonstrated only some clinical or pathologic evidence of recurrence which could not be distinguished from acute vascular rejection. Three patients had no sign of recurrence of the initial disease. The 1-year graft survival rate was 63% and the 5-year graft survival rate was 18.5%. In the group of patients with proven or possible recurrence (n = 13), the 1-year and 5-year graft survival rates were 49% and less than 10%, respectively. The recurrence was an early event, occurring before the end of the first month after transplantation in half the cases. The recurrence rate was 92% in non-nephrectomized patients and 50% in patients with bilateral nephrectomy. In the literature, 71 adult patients with primary HUS had received a total of 90 kidney grafts. Among them, 54% had a recurrence on their graft, which was diagnosed in 52% of the kidney transplants. It is note-worthy that when data from the literature are pooled with our results, the rate of recurrence appears to be significantly lower in binephrectomized patients than in patients with their native kidneys at the time of transplantation (5 of 14 versus 27 of 35 patients, respectively, p = 0.0155). By univariate analysis, no other risk factor for recurrence could be identified. Treatment with cyclosporine A did not influence the recurrence rate. We conclude that recurrence of HUS after renal transplantation is a frequent, early, and severe complication, leading rapidly to graft loss. Prospective studies are needed to confirm that bilateral nephrectomy prior to transplantation decreases the rate of recurrence.

In the James Bay region of Canada, with the advent of extensive hydroelectric development, methylmercury contamination of fish has become a serious problem, having a direct impact on the Cree way of living. In 1982, the Cree Board of Health and Social Services of James Bay implemented a methylmercury exposure surveillance program in all Cree communities. Since that time, it has developed several educational tools on methylmercury contamination, including posters, pamphlets, and a video. In 1993 and 1994, Cree leaders, Community Health Representatives, medical staff, and other selected band members were consulted to identify the needs of the population regarding information on mercury. All questions and comments were listed, and a summary was sent to those consulted to double check the type of information required by the population. This led to the preparation of a brochure on mercury in a question and answer format, as well as creation of posters. The brochure and the posters were published in French, English and Cree and distributed in each community. A radio message was broadcast in all communities, and individual and group meetings were also held. Cree involvement in the mercury information program has been essential to its success.

Most proteases a receptor or a binding site that serves to concentrate the proteolytic activity on the cell surface and to mediate cellular effects. We looked for such a receptor for renin, an aspartyl protease. The binding of recombinant human renin labelled with 125I was studied on primary and immortalized human mesangial cells. The binding of renin was specific, saturable and was characterized by Kd = 0.4 nM and 8,000 sites/cell and Kd = 1 nM and 2,000 sites/cell for primary and immortalized cells, respectively. The binding did not depend on the active site of the enzyme, was not followed by internalization and degradation of renin and did not modify intracellular Ca2+. Stimulation of primary cells with 100 nM induced a significant increase of 3H thymidine incorporation but was not associated with an increase of the cell number. Furthermore, incubation of mesangial cells 24 h with 100 nM renin provoked an increase of tPA and of PAI1 in the conditioned medium. This increase was not modified neither by captopril nor by angiotensin II receptors antagonists. The tPA antigen elevation was confirmed by fibrin zymography showing an increase of tPA/PAI1 complexes. But, surprisingly, the reverse zymogram showed that PAI antigen increase was associated with decreased PAI activity which was due to PAI clivage in an inactive form. PAI clivage by renin required the presence of the cells and could not be obtained by incubating renin and recombinant human PAI alone. When primary mesangial cells were cultured in the presence of a specific inhibitor of renin active site, RO 42-5982, PAI accumulation in the conditioned medium was reduced by 50-60%, suggesting that endogenous renin plays a role in PAI synthesis and/or secretion. The binding of renin does not induce cAMP and cGMP generation. However, in the presence of renin (100 nM and 1 microM) the extent of cGMP generated by CNP (10 and 100 nM) was reduced by 50%. Preliminary results of the renin receptor purification by affinity chromatography indicate that the receptor Mr is about 57 kDa.